As is well known in the art, delivery of pharmacological agents (or drugs) to a specific organ or tissue can be achieved through systemic or local administration. In systemic administration, the agent is introduced into the systemic, or general, circulation by ingestion, injection, inhalation and trans-dermal or trans-mucosal administration by local application of drops or ointments. Circulating blood delivers the agent to the target tissue by either passive or active transport.
Advantages of systemic administration are that this mode of administration, especially by ingestion, is simple and well accepted by the patient. A disadvantage, however, is that the agent must be administered at relatively high doses in order to reach the target area in sufficient quantity. Moreover, the agent is delivered to the entire body, which can include sites where the agent can cause significant side effects. This is especially true for chemotherapeutic agents that tend to present significant systemic toxicity, and steroids, which present significant long-term systemic side effects.
Another significant disadvantage of systemic administration is that transfer of many pharmacological agents from the blood to certain tissues, such as the brain or an eye, is very inefficient.
An alternative to systemic administration is to administer the pharmacological agent(s) into a target organ (or tissue) or in close proximity thereto. However, as is well known in the art, local administration of an agent into or proximate an organ; particularly, an eye, typically requires strict adherence to numerous safeguards.
As discussed in detail herein, the eye is a delicate and complex sense organ that is surrounded by specialized structures and protected by the orbit bones, soft tissues and eyelids. Because of the complex nature of the eye, it is susceptible to a large number of abnormalities (and/or diseases). The abnormalities include dry eye, allergies, infections, various inflammatory diseases and glaucoma.
Treatments of the abnormalities and diseases have, in general, been limited to topical administration of agents or preparations. A conventional example of topical administration of an agent to the eye is the delivery of timolol via eye drops.
As is well known in the art, eye drops facilitate transmission of the agent directly to the anterior part of the eye by instillation of the agent into the cul-de-sac. The agents are then moved via the tears of the eye across the cornea and sclera into the anterior and posterior chambers of the eye without initially entering the systemic circulation path.
The advantage of this mode of administration (or delivery) is that the agent is concentrated in the target tissue with a much lower systemic exposure. This tends to reduce the above-mentioned systemic effects.
A disadvantage of this mode of administration is that not all eye tissues are accessible by this route of delivery. Tears can also redirect a significant portion of the agent away from the target area relatively quickly.
A further disadvantage of this mode of administration is that it is mostly applicable to small molecular weight pharmacological agents. Indeed, large molecular weight agents, such as antibodies, are known to diffuse poorly across the cornea or the sclera.
Although jet injection devices have been employed for injecting pharmacological agents or medication inside the eye, there are no known references disclosing trans-mucosal delivery of pharmacological agents into the sub-mucosal spaces in the eye, mouth, nose, throat, esophagus, urethra, bladder or vagina.
Further, even when jet injection devices are employed to administer pharmacological agents or medication inside the eye, there are several drawbacks and disadvantages associated therewith. A significant disadvantage is that the conventional jet injection devices do not include a transfer mechanism that is adapted to provide safe, accurate, consistent and rapid delivery of pharmacological agents into the eye; particularly, a sub-mucosal compartment in the eye.
Further significant disadvantages are (i) the conventional jet injection transfer mechanism typically include a rigid, substantially linear delivery member, which in many instances restricts access into a sub-mucosal compartment, and (ii) the jet injection devices do not include any means of ensuring perpendicular placement of the surface of an organ, e.g., eye, which is an important factor to achieve effective agent delivery to an organ's mucosa.
Sub-mucosal injection using a conventional needle is also painful and each injection requires several steps to prepare the eye and safely perform the injection. The time required to perform injections can thus disrupt office schedules, resulting in unexpected prolongation of patient waiting times.
Associated with the development of new pharmacological treatments for retinal corneal, glaucoma, ENT, gum, urethra, bladder, vaginal and other diseases, specialists are being faced with the responsibility for meeting the ever increasing demand for delivery of pharmacological agents to an organ; particularly, an organ's mucosa and/or sub-mucosal compartment. Several devices and techniques, such as topical application of pharmacological agents on the mucosa, to delivery pharmacological agents to an organ have thus been employed. There are, however, similarly several drawbacks and disadvantages associated with this mode of administration.
By way of example, it is well known in the art that topical application of pharmacological agents on the mucosa is, in many instance, not very effective since the agent has a limited efficacy period, i.e. will generally not last for a long period of time. Slow release pharmacological agents, such as nano-particles, microspheres and liposome, similarly have a limited efficacy period.
It would therefore be desirous to provide an improved agent delivery apparatus and associated method to standardize and simplify the sub-mucosal agent delivery process, improve patient comfort and safety, and increase efficiency of the process.
It is therefore an object of the present invention to provide an agent delivery method and system that provides safe, accurate, consistent, and rapid delivery of pharmacological or therapeutic agents into the sub-mucosal compartment of organs.
It is another object of the present invention to provide a sub-mucosal agent delivery method and system that facilitates minimally invasive delivery of therapeutic agents into the sub-mucosal compartment of organs with minimal risk of trauma and infection.
It is another object of the present invention to a sub-mucosal agent delivery method and system that facilitates delivery of therapeutic agents into the subconjunctival, retrobulbar, subtenon, intrascleral and subchoroidal compartments of the eye and/or behind the lid thereof.